In general, when there is a report on a substance or a compound having an antitumor activity and the report is based solely on in vitro results, it has been pointed out that such reported results do not directly suggest in vivo results. In other words, a substance showing an antitumor activity in vitro does not necessarily show an antitumor activity in vivo, and application of a substance showing an antitumor activity in vitro directly as an antitumor agent is difficult.
For example, it has been reported that a compound represented by the formula (I)

(hereinafter to be also referred to as compound A; SEQ ID NO: 1), particularly a stereoisomer of the formula (II)

(hereinafter to be also referred to as compound B or FK228), selectively inhibits histone deacetylase to derive a potent antitumor activity, and that this substance causes high acetylation of histone in the treated cells, thereby inducing transcription-regulatory activity of various genes, cell cycle inhibitory activity and apoptosis (e.g., JP-B-7-64872 (corresponding to U.S. Pat. No. 4,977,138), “Experimental Cell Research”, US (1998), vol. 241, pp. 126–133). As the situation now stands, however, there are many problems yet to be solved, such as whether or not in vitro results are directly applicable in vivo, whether or not a useful in vivo effect can be afforded in any tumor, and the like. No report has ever verified in vitro and in vivo antitumor activities against soft tissue sarcoma (particularly synovial sarcoma) of the present invention.
Histone deacetylase is a metallo-deacetylating enzyme coordinating Zn at an active center (M. S. Finnin et al., Nature, 401, 188–193 (1999)). This enzyme is considered to change affinity of various acetylated histones for DNA. The direct biological phenomenon brought thereby is a change in the chromatin structure. The minimum unit of the chromatin structure is a nucleosome wherein 146 bp DNA is wound 1.8 times anticlockwise around a histone octamer (H2A, H2B, H3 and H4, each 2 molecules, core histone). The core histone stabilizes the nucleosome structure by interaction of the positive charge of the N-terminus of each histone protein with DNA. Acetylation of histone is controlled by the equilibrium between an acetylation reaction involving histone acetyltransferase and a deacetylation reaction involving histone deacetylase. It is considered that the histone acetylation occurs at a lysin residue where the histone protein N-terminus is evolutionally preserved well, due to which a core histone protein loses charges at the N-terminus, interaction with DNA is attenuated, and the structure of nucleosome becomes unstable. Accordingly, the histone deacetylation is considered to be the reverse thereof, namely, a shift toward stabilization of the nucleosome structure. However, to what degree the acetylation changes the chromatin structure and how it relates to the transcriptional regulation etc. secondarily induced thereby are unclear in many aspects.
As genetic characteristics of synovial sarcoma, it has been reported that, in about 97% of the entire synovial sarcomas, SYT gene present in the 18th chromosome and SSX gene present on the X chromosome are fused due to chromosomal translocation t (18,X) to express a chimera protein called SYT-SSX, and SYT protein constituting the N-terminal region of this protein is bound with a chromatin remodeling-associated protein such as p300 and BRM to form a complex (Josiane E. Eid et al., Cell, 102, 839–848 (2000)). Synovial sarcoma is one kind of soft tissue sarcoma developed in the four limbs and trunk of the body of males and females, and its primary therapy includes removal of tumor by operation and chemotherapy before and after the operation. However, chemotherapy is associated with poor prognosis and a five-year survival rate is about 60–70%. Thus, an effective cure has not been established as yet.